Major histocompatibility ubiquitinated

Bartee, E., et ah, Downregulation of major histocompatibility complex class I by human ubiquitin ligases related to viral immune evasion proteins. J Virol, 2004, 78(3), 1109-20. 

Proteasomes of Thermoplasma contain a single type of p subunit but eukaryotic proteasomes contain subunits with at least three distinct substrate preferences.347 M9c They all appear to use the same hydrolytic mechanism but in their substrate specificities they are chymotrypsin-like, peptidylglutamyl-peptide hydrolyzing, branched chain amino acid preferring, and small neutral amino acid preferring based on the P, amino acid residue. In the spleen some of the P subunits of the proteasomes appear to have been replaced by proteins encoded by the major histocompatibility complex of the immune system (Chapter 31).347 This may alter the properties of the proteasome to favor their function in antigen processing. Proteasomes are also ATP- and ubiquitin-dependent, as discussed in Section 6. 

The immune system also makes use of the ubiquitin-mediated pathway in the response to altered self-cells, particularly virus-infected cells. Viral proteins within the cytosol of infected cells are ubiquitinated and then degraded in pro-teasomes specially designed for this role. The resulting antigenic peptides are transported to the endoplasmic reticulum, where they bind to class I major histocompatibility complex (MHC) molecules within the ER membrane. Subsequently, the peptide-MHC complexes move to the cell membrane where the antigenic peptides can be recognized by c3rt otoxic T lymphocytes, which mediate the destruction of the Infected cells. 

Proteasomes are the major cytosolic and nuclear protein degradation machineries and they are also responsible for the proteolysis of misfolded, ER-dislocated (endoplasmic reticulum) proteins [1-3]. Proteasomal protein turnover takes place in an ubiquitin-dependent manner. The proteasome-generated products - ohgopeptides varying in length from 3 to up to 30 amino acid residues - are further processed by aminopeptidases. In higher vertebrates, antigenic peptides are selected from the peptide pool produced by proteasomes and downstream aminopeptidases for presentation on the outer cell surface by major histocompatibility class 1 (MHCl) protein complexes. In this way, proteasomes are essential factors in the detection and eradication of virally infected cells. 

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